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Background/aim: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance., Patients and Methods: This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes., Results: The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC., Conclusion: This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Our objectives in this study were to (i) evaluate the clinical significance of X-box-binding protein 1 (XBP1) expression in cases of hepatocellular carcinoma (HCC) and (ii) assess the potential of XBP1 to be used as a prognostic biomarker., Patients and Methods: The expression of XBP1 protein in 267 HCC tissue specimens was measured using immunohistochemistry in order to characterize the associations among XBP1 expression, clinicopathological factors and survival outcomes. Survival analysis using follow-up data was used to assess the prognostic value of XBP1 in cases of HCC. Immunohistochemistry revealed a significant decrease in cytoplasmic XBP1 protein expression in HCC tumor tissue., Results: Immunoreactivity results showed that low cytoplasmic XBP1 expression was significantly associated with vascular invasion, as well as poor 5-year overall survival and long-term disease-specific (DSS) and disease-free (DFS) survival rates. Kaplan-Meier survival curves further confirmed a significant association between low cytoplasmic XBP1 protein expression and poor DSS and DFS. Univariate and multivariate analyses revealed that XBP1 expression, tumor differentiation, vascular invasion, tumor stage, and the rate of recurrence were linked to DSS, while low cytoplasmic XBP1 expression remained an independent predictor of poor DSS. Our analysis also revealed that XBP1 expression, tumor differentiation, vascular invasion, and T classification were linked to DFS, while low cytoplasmic XBP1 expression remained an independent predictor of poor DFS., Conclusion: Low cytoplasmic XBP1 protein expression may play an important role in the pathogenesis of HCC, which suggests that XBP1 could potentially be targeted to benefit therapeutic strategies for HCC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Oral squamous cell carcinoma (OSCC) is the most common malignant cancer, with high mortality rates in advanced stages. Recent studies have shown that the expression of ALPK1 mRNA and its inhibitory differentiation function are associated with cancer progression. However, the expression and clinicopathologic features of ALPK1 in OSCC remain unexplored. Herein, the authors investigated the expression patterns of ALPK1 in 39 matched OSCC patients and examined the relationship between ALPK1 protein expression and clinicopathologic factors using immunohistochemical scores. Using Western blot analysis, ALPK1 expression was found to be significantly higher in tumor tissues than that in nontumor tissues. Through an immunoreactive scoring system, a significantly higher number of advanced-stage tumor size T4 and lymph node metastasis N2 exhibited higher ALPK1 expression levels than that exhibited by T1/T2/T3 tumors and N0/N1. In addition, ALPK1 protein expression was aberrant in malignant oral cancer cell lines compared with that in pre-malignant oral epithelial cells, whereas minimal expression was observed in normal oral epithelial cells. Knockdown of ALPK1 resulted in a significant reduction in cell growth, migration, and invasion capacity in vitro. Consequently, expression of N-cadherin and vimentin decreased in ALPK1-deficient cells. Thus, these results suggest that ALPK1 serves as a potential biomarker and target for OSCC development in late stages., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: Lung adenocarcinoma is a non-small cell lung cancer, a common cancer in both genders, and has poor clinical outcome. Our aim was to evaluate the role of epidermal growth factor (EGF)-like domain multiple 6 (EGFL6) and its prognostic significance in lung adenocarcinoma., Methods: EGFL6 expression was studied by immunohistochemical staining of specimens from 150 patients with lung adenocarcinoma. The correlation between clinicopathological features and EGFL6 expression was quantitatively analysed. We used Kaplan-Meier analysis and Cox proportional hazard models to examine the prognostic value of EGFL6 in terms of overall survival., Results: No significant correlation was found between EGFL6 expression and clinical parameters. However, patients with high levels of EGFL6 expression showed a tendency towards poor prognosis, with borderline statistical significance. Grouping the patients according to a medium age value revealed a significant association between high EGFL6 expression and poor clinical outcome in young patients. This finding was further confirmed by grouping the patients into three groups according to age. HR in patients with high EGFL6 expression was higher in younger patients than in older patients., Conclusion: High EGFL6 expression may serve as a marker for poor prognosis of lung adenocarcinoma, especially in younger patients., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Circulating tumor cells (CTCs) in peripheral blood is an indication of poor prognosis for patients with different cancer types. However, most of the available technologies for detecting CTCs show low sensitivity and specificity. Therefore, we attempted to find an alternative marker for CTCs of colorectal cancer. We have directly extracted RNA from CTCs contained in 1.5 mL peripheral blood from 90 colorectal cancer patients and 151 healthy donors, and screened these samples for candidate marker genes by nested real-time quantitative polymerase chain reaction (PCR). From genes selected from a public database of microarray analyses, we successfully identified epithelial cell transforming sequence 2 oncogene ( ECT2 ) as a gene that exhibits high differential expression ratios ( p < 0.01). ECT2 displays good sensitivity and specificity, with an area under the curve (AUC) value of 0.821. This marker gene also has a high detection rate in patients with serum carcinoembryonic antigen (CEA) concentrations below the diagnostic threshold of 5 ng/mL. The expression of ECT2 can therefore serve as an alternative measurement that can compensate for the inadequacy of the current CEA test in the diagnosis and monitoring of colorectal cancer patients.

Oral cancer is a common cancer with poor prognosis. We evaluated the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) and its prognostic significance in oral cancer. PBK/TOPK expression was measured by immunohistochemical staining of samples from 287 patients with oral cancer. The association between PBK/TOPK expression and clinicopathological features was analyzed. The prognostic value of PBK/TOPK for overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. A high PBK/TOPK expression level was correlated with long overall survival. The prognostic role of PBK/TOPK expression was significant in young patients (p < 0.05), patients with smoking habits (p < 0.05), and late stage disease (p < 0.05). Our results suggest that PBK/TOPK expression is enhanced in oral cancer. High PBK/TOPK expression, either alone or in subgroups according to clinicopathological features, may serve as a favorable prognostic marker for patients with oral cancer.